Preliminary construction of non-coding RNAs and ceRNA regulatory networks mediated by exosomes in porcine follicular fluid.

BACKGROUND: Follicles are fundamental units of the ovary, regulated intricately during development. Exosomes and ovarian granulosa cells (OGCs) play pivotal roles in follicular development, yet the regulatory mechanisms governing exosomes remain elusive. RESULTS: High-throughput sequencing was employed to evaluate the complete transcript expression profiles of six samples (three porcine ovarian granulosa cells-exosome co-culture samples (GCE) and three porcine ovarian granulosa cells (POGCs) samples). Differential expression analysis revealed 924 lncRNAs, 35 circRNAs, 49 miRNAs, and 9823 mRNAs in the GCE group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated enrichment of differentially expressed transcripts in pathways related to cell proliferation and apoptosis. Furthermore, a ceRNA regulatory network comprising 43 lncRNAs, 6 circRNAs, 11 miRNAs, and 126 mRNAs was constructed based on intergene co-expression correlations. Seven miRNAs associated with cell proliferation and apoptosis regulation were identified within this network, encompassing 92 subnet pairs as candidate genes for further exploration of exosome regulatory mechanisms. Additionally, preliminary verification at the cellular level demonstrated that exosomal miR-200b enhances the viability of POGCs. CONCLUSIONS: Transcriptome analysis unveiled a pivotal candidate ceRNA network potentially implicated in exosome-mediated regulation of granulosa cell proliferation and apoptosis, thereby influencing porcine follicular development. These findings offer insights into the molecular mechanisms of follicular fluid exosome regulation, encompassing both coding and non-coding RNA perspectives.

Genetic Screening of Factors in the Plant Protein Secretion.

The endomembrane system in plants is composed of interconnected membrane organelles that contribute to intracellular structure and function. These organelles include the endoplasmic reticulum (ER), Golgi apparatus, vacuole, trans-Golgi network, and prevacuolar compartment or multivesicular body. Through vesicle-mediated transport, secreted proteins are synthesized in the ER and subsequently transported along the secretory pathway to the vacuole or outside of cells to fulfill specialized functions. Genetic screening is a crucial method for studying plant protein secretion. It entails identifying phenotypic differences resulting from genetic mutations, such as ethyl methanesulfonate, T-DNA insertion, and RNAi, to investigate gene function and discover mutants with specific traits or gene functions. Significant progress has been achieved in the study of plant protein secretion through genetic screening. In this protocol, we provide a step-by-step guide to studying the protein secretion pathway using a genetic screen approach. We use the example of the free 1 suppressor of Arabidopsis thaliana and oil body mutants of Marchantia polymorpha. Additionally, we offer an overview of genetic screening and briefly summarize the emerging technologies in the field of protein secretion research.

Conjoint analysis of succinylome and phosphorylome reveals imbalanced HDAC phosphorylation-driven succinylayion dynamic contibutes to lung cancer.

Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming.

Comparative Analysis of the Ovary Transcriptome among Wanyue Black and Yorkshire Gilts Using RNA-Seq.

Pubertal genetic variations between the indigenous Chinese Wanyue Black pig breed and the imported Yorkshire breed significantly impact their reproductive capacity. In order to identify the differentially expressed genes, gene networks, and metabolic pathways in ovary transcriptome of gilts, the serum hormone levels were analyzed by ELISA, and RNA-seq was performed to analyze ovarian genes. Our results reveal higher estradiol (E2) levels in Wanyue black gilts compared to Yorkshire gilts, while Yorkshire gilts exhibit elevated progesterone (P4) and GnRH levels. We identified a total of 154 differentially expressed genes (DEGs), with 87 up-regulated and 67 down-regulated genes in the Wanyue black gilts ovaries compared to the Yorkshire gilts. GO enrichment analysis unveiled the participation of DEGs in processes such as "Reproduction", "Reproductive system development", and "Ovarian follicle development". Moreover, KEGG enrichment analysis revealed the involvement of DEGs in multiple signaling pathways associated with hormone biosynthesis and puberty, encompassing "Steroid hormone biosynthesis", "Estrogen signaling pathway", and "Prolactin signaling pathway". The subsequent bioinformatics analysis identified nine functional genes that potentially contribute to the disparity in ovaries between Wanyue black gilts and Yorkshire gilts. This study offers significant insights into the endocrine and genetic aspects of pubertal development in gilts.

Immunosuppression induces regression of fibrosis in primary biliary cholangitis with moderate-to-severe interface hepatitis.

BACKGROUND: In patients with primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA), the presence of moderate-to-severe interface hepatitis is associated with a higher risk of liver transplantation and death. This highlights the need for novel treatment approaches. In this study, we aimed to investigate whether combination therapy of UDCA and immunosuppressant (IS) was more effective than UDCA monotherapy. METHODS: We conducted a multicenter study involving PBC patients with moderate-to-severe interface hepatitis who underwent paired liver biopsies. Firstly, we compared the efficacy of the combination therapy with UDCA monotherapy on improving biochemistry, histology, survival rates, and prognosis. Subsequently we investigated the predictors of a beneficial response. RESULTS: This retrospective cohort study with prospectively collected data was conducted in China from January 2009 to April 2023. Of the 198 enrolled patients, 32 underwent UDCA monotherapy, while 166 received combination therapy, consisting of UDCA combined with prednisolone, prednisolone plus mycophenolate mofetil (MMF), or prednisolone plus azathioprine (AZA). The monotherapy group was treated for a median duration of 37.6 months (IQR 27.5-58.1), and the combination therapy group had a median treatment duration of 39.3 months (IQR 34.5-48.8). The combination therapy showed a significantly greater efficacy in reducing fibrosis compared to UDCA monotherapy, with an 8.3-fold increase in the regression rate (from 6.3% to 52.4%, P < 0.001). Other parameters, including biochemistry, survival rates, and prognosis, supported its effectiveness. Baseline IgG >1.3 × ULN and ALP <2.4 × ULN were identified as predictors of regression following the combination therapy. A predictive score named FRS, combining these variables, accurately identified individuals achieving fibrosis regression with a cut-off point of ≥ -0.163. The predictive value was validated internally and externally. CONCLUSION: Combination therapy with IS improves outcomes in PBC patients with moderate-to-severe interface hepatitis compared to UDCA monotherapy. Baseline IgG and ALP are the most significant predictors of fibrosis regression. The new predictive score, FRS, incorporating baseline IgG and ALP, can effectively identify individuals who would benefit from the combination therapy.

Genomic profiling and associated B cell lineages delineate the efficacy of neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoimmunotherapy has offered novel therapeutic options for patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Depicting the landscape of genomic and immune profiles is critical in predicting therapeutic responses. METHODS: We integrated whole-exome sequencing, single-cell RNA sequencing, and immunofluorescence data of ESCC samples from 24 patients who received neoadjuvant treatment with PD-1 inhibitors plus paclitaxel and platinum-based chemotherapy to identify correlations with therapeutic responses. FINDINGS: An elevation of small insertions and deletions was observed in responders. DNA mismatch repair (MMR) pathway alternations were highly frequent in patients with optimal responses and correlated with tumour infiltrating lymphocytes (TILs). Among the TILs in ESCC, dichotomous developing trajectories of B cells were identified, with one lineage differentiating towards LMO2+ germinal centre B cells and another lineage differentiating towards CD55+ memory B cells. While LMO2+ germinal centre B cells were enriched in responding tumours, CD55+ memory B cells were found to correlate with inferior responses to combination therapy, exhibiting immune-regulating features and impeding the cytotoxicity of CD8+ T cells. The comprehensive evaluation of transcriptomic B cell lineage features was validated to predict responses to immunotherapy in patients with cancer. INTERPRETATION: This comprehensive evaluation of tumour MMR pathway alternations and intra-tumoural B cell features will help to improve the selection and management of patients with ESCC to receive neoadjuvant chemoimmunotherapy. FUNDING: National Science Foundation of China (82373371, 82330053), Eastern Scholar Program at Shanghai Institutions of Higher Learning, National Science and Technology Major Project of China (2023YFA1800204, 2020YFC2008402), and Science and Technology Commission of Shanghai Municipality (22ZR1410700, 20ZR1410800).

Disease Burden and Prediction Analysis of Tracheal, Bronchus, and Lung Cancer Attributable to Residential Radon, Solid Fuels, and Particulate Matter Pollution Under Different Sociodemographic Transitions From 1990 to 2030.

BACKGROUND: This study investigated the impact of epidemiologic and sociodemographic changes in tracheal, bronchus, and lung cancer associated with residential radon, solid fuels, and particulate matter. RESEARCH QUESTION: What are the influencing factors of tracheal, bronchus, and lung cancer disease burden attributable to the three pollutants? STUDY DESIGN AND METHODS: Data were obtained from the Global Burden of Disease 2019. Age-standardized mortality rate (ASMR) and sociodemographic index (SDI) values were collected from 21 regions, and restricted cubic splines and quantile regression were used to investigate the relationship between ASMR or age-standardized disability-adjusted life years rate (ASDR), and SDI. Additionally, five countries with different SDIs were selected, and the Bayesian age-period-cohort model was used to predict the ASMR trends from 2020 to 2030. RESULTS: High SDI quintiles were associated with increased residential radon pollution. The disease burden attributed to these three pollutants was particularly severe in the middle SDI quintiles. Older adults aged 80 to 89 years had the highest age-specific mortality, and the disease burden was greater in male patients than in female patients with these cancers attributed to the pollutants. The highest ASMR attributable to particulate matter when the SDI was 0.7. As the SDI increased, the disease burden caused by radon increased, whereas the burden caused by solid fuels decreased. Projections have indicated a rise in the death burden in patients with this cancer from particulate pollution in China, India, and Uganda over the next decade. INTERPRETATION: The disease burden of tracheal, bronchus, and lung cancer attributed to the three pollutants was influenced by SDI, sex, and age. Older men are more susceptible to be affected. More preventive interventions may be required for men at younger ages to reduce the high death burden of older men. However, it is necessary to give due attention to women in specific countries in the future.

FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response.

Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.

The mortality of oral cancer attributable to tobacco in China, the US, and India.

PURPOSE: Assessing the mortality rates associated with tobacco-related oral cancer (OC) is crucial for effective allocation of resources within healthcare and economic systems. METHODS: In this study, data from the Global Burden of Disease Study (GBD) 2019 were utilized to analyze the burden of tobacco-attributable OC in China, the United States (US), and India from 1990 to 2019. Descriptive statistics and an age-period-cohort model were employed to examine and compare the effects on OC mortality. RESULTS: 1. Attributable to tobacco, the deaths remained stable in the US, but increased in China and India. The trend of age-standardized mortality rate of OC increased in China, and decreased in the US and India, whereas the rate in India was the highest. 2. According to the APC model, the risk of death increased with age in all three countries. The period and later birth cohort effects were identified as risk factors in China and India, while in the US, the previous cohorts were identified as a risk factor. Except for India, males faced higher death risk than females in China and the US. CONCLUSIONS: The burden of OC attributable to tobacco remains substantial in China and India. Public health officials in these countries should implement prevention and treatment strategies for OC, and interventions aimed at regulating the tobacco industry. The elderly is at an elevated risk for OC, and medical resources and policies should be directed toward this population. The successes experience in tobacco control and OC prevention in the US may serve as a model for other countries.

Progress in construction and release of natural polysaccharide-platinum nanomedicines: A review.

Natural polysaccharides are natural biomaterials that have become candidate materials for nano-drug delivery systems due to their excellent biodegradability and biocompatibility. Platinum (Pt) drugs have been widely used in the clinical therapy for various solid tumors. However, their extensive systemic toxicity and the drug resistance acquired by cancer cells limit the applications of platinum drugs. Modern nanobiotechnology provides the possibility for targeted delivery of platinum drugs to the tumor site, thereby minimizing toxicity and optimizing the efficacies of the drugs. In recent years, numerous natural polysaccharide-platinum nanomedicine delivery carriers have been developed, such as nanomicelles, nanospheres, nanogels, etc. Herein, we provide an overview on the construction and drug release of natural polysaccharide-Pt nanomedicines in recent years. Current challenges and future prospectives in this field are also put forward. In general, combining with irradiation and tumor microenvironment provides a significant research direction for the construction of natural polysaccharide-platinum nanomedicines and the release of responsive drugs in the future.

Collaborative Innovation Strategy of Supply Chain in the Context of MCU Domestic Substitution : A Differential Game Analysis.

The domestic substitution of the IC (the Integrated Circuit) industry improves economic efficiency and is significant in ensuring national security, which has gradually become an essential strategy for countries worldwide. Based on the background of domestic substitution of integrated circuits, we select a typical component Micro Controller Unit) as the research object, construct a three-level supply chain game model under different scenarios in a dynamic architecture, and analyze the game problem of collaborative innovation of the MCU supply chain. We fully consider the impact of factors such as time, cost and the innovation and collaborative innovation efforts of various supply chain members on the level of domestic substitution. Moreover, we put forward a two-part pricing + cost-sharing contract to achieve supply chain coordination. We found that: (1) Collaborative innovation of the supply chain in the centralized decision-making scenario achieves the highest level, followed by the cost-sharing scenario; (2) The two-part pricing + cost-sharing contract can help achieve supply chain coordination; (3) The trend of the MCU domestic substitution level with manufacturing cost is U-shaped, which means the increase of manufacturing cost may have a positive impact on the process of domestic substitution.

Disability weight measurement for the severity of different diseases in Wuhan, China.

BACKGROUND: Measurement of the Chinese burden of disease with disability-adjusted life-years (DALYs) requires disability weight (DW) that quantify health losses for all non-fatal consequences of disease and injury. The Global Burden of Disease (GBD) 2013 DW study indicates that it is limited by lack of geographic variation in DW data and by the current measurement methodology. We aim to estimate DW for a set of health states from major diseases in the Wuhan population. METHODS: We conducted the DW measurement study for 206 health states through a household survey with computer-assisted face-to-face interviews and a web-based survey. Based on GBD 2013 DW study, paired comparison (PC) and Population health equivalence (PHE) method was used and different PC/PHE questions were randomly assigned to each respondent. In statistical analysis, the PC data was analyzed by probit regression. The probit regression results will be anchored by results from the PHE data analyzed by interval regression on the DW scale units between 0 (no loss of health) and 1 (loss equivalent to death). RESULTS: A total of 2610 and 3140 individuals were included in the household and web-based survey, respectively. The results from the total pooled data showed health state "mild anemia" (DW = 0.005, 95% UI 0.000-0.027) or "allergic rhinitis (hay fever)" (0.005, 95% UI 0.000-0.029) had the lowest DW and "heroin and other opioid dependence, severe" had the highest DW (0.699, 95% UI 0.579-0.827). A high correlation coefficient (Pearson's r = 0.876; P < 0.001) for DWs of same health states was observed between Wuhan's survey and GBD 2013 DW survey. Health states referred to mental symptom, fatigue, and the residual category of other physical symptoms were statistically significantly associated with a lower Wuhan's DWs than the GBD's DWs. Health states with disfigurement and substance use symptom had a higher DW in Wuhan population than the GBD 2013 study. CONCLUSIONS: This set of DWs could be used to calculate local diseases burden for health policy-decision in Wuhan population. The DW differences between the GBD's survey and Wuhan's survey suggest that there might be some contextual or culture factors influencing assessment on the severity of diseases.

Mortality and Years of Life Lost Due to Brain and Other Central Nervous System Cancer in Wuhan, China, from 2010 to 2019.

BACKGROUND: Brain cancer is one of the worst types of cancer worldwide. Understanding the epidemiology of CNS cancer is critical for properly allocating healthcare resources. METHODS: We collected data on CNS cancer deaths in Wuhan, China, during 2010-2019. We constructed the cause-eliminated life tables to calculate life expectancy (LE), mortality, and years of life lost (YLLs) by age and sex. The BAPC model was used to forecast the future trends of age-standardized mortality rate (ASMR). Decomposition analysis was adopted to explore the contribution of population growth, population aging, and age-specific mortality to the change in total CNS cancer deaths. RESULTS: In 2019, the ASMR of CNS cancer was 3.75, and the ASYR was 135.70 in Wuhan, China. ASMR was expected to decrease to 3.43 in 2024. The age distribution of deaths due to CNS cancer was concentrated in the middle-aged and older population, with a peak in the 65-69 age group. Caidian, Jianghan, and Qingshan had the greatest ASMRs in 2019 in Wuhan, with ASMRs of 6.32, 4.78, and 4.75, respectively. Population aging is critical to the change in total CNS cancer deaths. CONCLUSION: We analyzed the current status, temporal trends, and gender and age distributions of the burden of CNS cancer in Wuhan, during 2010-2019, providing a valuable reference for better lessening the CNS cancer burden.

Ten-eleven translocation-2 inactivation restrains IL-10-producing regulatory B cells to enable antitumor immunity in hepatocellular carcinoma.

BACKGROUND AND AIMS: IL-10-producing regulatory B cells (IL-10 + B cells), a dominant regulatory B cell (Breg) subset, foster tumor progression. However, the mechanisms underlying their generation in HCC are poorly understood. Ten-eleven translocation-2 (TET2), a predominant epigenetic regulatory enzyme in B cells, regulates gene expression by catalyzing demethylation of 5-methylcytosine into 5-hydroxymethyl cytosine (5hmC). In this study, we investigated the role of TET2 in IL-10 + B cell generation in HCC and its prospects for clinical application. APPROACH AND RESULTS: TET2 activation in B cells triggered by oxidative stress from the HCC microenvironment promoted IL-10 expression, whereas adoptive transfer of Tet2 -deficient B cells suppressed HCC progression. The aryl hydrocarbon receptor is required for TET2 to hydroxylate Il10 . In addition, high levels of IL-10, TET2, and 5hmc in B cells indicate poor prognosis in patients with HCC. Moreover, we determined TET2 activity using 5hmc in B cells to evaluate the efficacy of anti-programmed death 1 (anti-PD-1) therapy. Notably, TET2 inhibition in B cells facilitates antitumor immunity to improve anti-PD-1 therapy for HCC. CONCLUSIONS: Our findings propose a TET2-dependent epigenetic intervention targeting IL-10 + B cell generation during HCC progression and identify the inhibition of TET2 activity as a promising combination therapy with immune checkpoint inhibitors for HCC.

A Pre-Generation of Emergency Reference Plan Model of Public Health Emergencies with Case-Based Reasoning.

Background and Purpose: In the early 21st century, the coronavirus alone has ravaged the world three times. Public health emergencies have caused a tremendous negative impact on public health, daily life, and global economic development, for having the characteristics of complexity and great harm. To tackle these problems, a pre-generation of emergency reference plan model of public health emergencies is proposed to better deal with the outbreak and spread of public health events. Methods: The method is divided into three stages. First, the modified SEIR model is used to predict the attribute values of the target case. Then, the similar case sets are extracted and filtered by calculating the similarity through the cross-efficiency evaluation method with the parallel system. Finally, the multi-stage emergency effect evaluation model is conducted so that the emergency plan with the best response effect at this stage can be made for reference. Results: We collected 25 typical events of COVID-19 that occurred in 11 cities in China as historical case bases and target cases, respectively. The result of the experiment verified the feasibility and effectiveness of the proposed method. Conclusion: This paper presents a new perspective on making a public health emergency plan, which could improve the decision-making accuracy and efficiency, maximize the emergency effect and save precious time for emergency response. This model can provide rapid decision supports for decision-making for public services such as government departments, centers for disease control, medical emergency centers and transport authorities, etc.

Yeast Probiotic and Yeast Products in Enhancing Livestock Feeds Utilization and Performance: An Overview.

The intensive use of antibiotics as growth-promoting agents in animal production has resulted in the spread of animal antibiotic resistance and possibly human antibiotic resistance. Based on this premise, it is significant to explore an alternative approach to preventing infectious diseases and promoting animal growth and health. Yeast as the main natural growth promoter in livestock nutrition has been extensively studied for decades. Numerous yeasts and yeast-containing products are produced, marketed, and used in animal feed as providers of nutrient sources, probiotics, and nutrients or serve distinct nutritional functions. A large amount of scientific research suggests that yeasts and their derivatives may be good for animal growth performance and health, especially when animals are housed in poor sanitation or are suffering from disease. However, when yeasts are used as a surrogate for livestock antibiotics, the results vary according to several factors, including yeast species, yeast product components, feed ingredients, animal category, type of symptoms, and differences in the rearing environment. In this review, the effects of different yeasts on different animals will be reviewed. The types of widely used yeast products, their functional characteristics, and application effects will be discussed in order to provide a reference for the development and application of yeast feed products.

Trends in Deaths Attributable to Smoking in China, Japan, United Kingdom, and United States From 1990 to 2019.

Objectives: This study aimed to estimate the long-term trends of deaths attributable smoking in China, Japan, the United Kingdom (UK) and the United States (US). Methods: Using 2000-2019 death data from Global Burden of Disease (GBD) 2019, we estimated age-period-cohort effects on smoking attributable mortality, and decomposed of differences in smoking-attributable deaths in 1990 and 2019 into demographic factors. Results: From 1990 to 2019, smoking-attributable deaths increased in China, which was due to population growth and demographic aging. From 1990 to 2019, both age-standardized smoking attributable mortality rates trended downward across countries. Among four countries, age rate ratios (RRs) for smoking-attributable mortality increased with age, while period and cohort RRs decreased with year. Conclusion: The age-standardized mortality rates, period effects and cohort effects of smoking attributable mortality in China, Japan, UK, and US have been declining in both sexes from 1990 to 2019, which suggests that smoke-free policies, help to quit tobacco use, improved health education, more accessible healthcare service, and increased taxes have been effective. Additionally, increased smoking attributable deaths in elderly should got more attention.

Comparison of trend in chronic kidney disease burden between China, Japan, the United Kingdom, and the United States.

Chronic kidney disease (CKD) caused heavy burden globally. This study aimed to investigate the patterns and temporal variations in the burden of CKD in China, Japan, the United Kingdom (U.K.), and the United States (U.S.) from 1990 to 2019, and decompose the difference in CKD disease burden between 1990 and 2019 into demographic factors. From 1990 to 2019, although the age-standardized rate (ASR) of incidence remained stable in the four countries, and the ASR of mortality and disability-adjusted life years (DALY) have declined in four countries (except for the increase in U.S.), the number of CKD incidence, death, and DALY increased significantly. The average disease burden per case in U.S. has increased between 1990 and 2019, with an increasing proportion of death-related disease burden. For the CKD due to diabetes and hypertension, whose incidences accounted for < 25% of the total CKD, while it accounts for more than 70% of the deaths (except in U.K. with 54.14% in women and 51.75% in men). CKD due to diabetes and hypertension should be the focus of CKD prevention and control. Considering the high treatment costs of CKD and ESRD, it is urgent and necessary to transform CKD treatment into primary and secondary prevention.

BIRC5 Modulates PD-L1 Expression and Immune Infiltration in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most prevalent thoracic cancer with the highest incidence and mortality worldwide. Baculoviral IAP Repeat Containing 5 (BIRC5) is well studied in many malignancies, its prognosis value and correlation with the tumor microenvironment (TME) in LAUD remains largely elusive. Methods: The Wilcoxon signed-rank test and logistic regression were used to evaluate the relationship between clinical features and BIRC5 expression in LUAD. To assess the impact of BIRC5 on prognosis, the Kaplan-Meier plotter analysis and Cox regression were used, as well as a receiver operating characteristic (ROC) curve and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were recruited to predict the association between BIRC5 and immune cell infiltrations. Furthermore, qRT-PCR and western bolt were utilized to confirm gene expression on mRNA and protein levels. The proliferation of A549 and H1299 cells was evaluated using CCK8 and EdU assay. Cell mobility was tested by transwell assay and wound healing assay. Detection of PD-L1 and infiltrated CD8 T cells in xenograft tumors was done by flow cytometry. Results: BIRC5 expression was found to be substantially greater in LUAD patients. According to KM-plotter analysis, patients with high levels of BIRC5 had shorter survival rates. Multivariate Cox analysis revealed that elevated BIRC5 expression was an independent risk factor for OS and PFS in LUAD patients. High BIRC5 expression was predicted to be associated with chemokine activity and immune cell chemotaxis, whereas ssGSEA suggested that BIRC5 is highly associated with CD8 T cell infiltration and PD-L1 levels. In vitro experiments suggested overexpression of BIRC5 promoted the proliferation, mobility, and PD-L1 level of A549 cells, and vice versa in H1299 cells. Furthermore, in vivo study suggested elevated tumor weight and PD-L1 levels in xenograft tumors generated from LLC cells with overexpressed BIRC5. Conclusion: BIRC5 promotes lung adenocarcinoma progression by modulating PD-L1 expression and inducing tumor immune evasion.